Science and discovery spurs clinical trial

CWRU researchers lay groundwork for joint effort with local hospitals

Arnold Caplan, a biology professor at Case Western Reserve University, had long studied mesenchymal stem cells, adult stem cells culled from bone marrow, as building blocks for engineered tissues and organs.

Robert Miller, a professor of neurosciences and vice dean for research at the Case Western Reserve University School of Medicine, had spent his career studying neural development, with a focus on treatments for multiple sclerosis.

They met at a Research Showcase in 2003 and decided they should work together.

“We knew MSCs differentiate into bone and tendon and other connective tissues, but we were just beginning to understand they also provide healing instructions at the site of injury,” Caplan, said.

Miller was looking for therapies for diseases that attack myelin, the protective coating that wraps nerves’ long axons.

In MS, the immune system attacks the myelin and the exposed nerves’ intricate wiring can be damaged. The result: nerve signals can be blocked, causing loss of balance and coordination, cognitive ability and other functions. Losses may become permanent.

“What the nerves need is repair and protection,” Miller said.

The researchers thought molecules MSCs make could be useful, but, “It was a shot in the dark,” Caplan said.

After some promising in vitro results, Caplan provided Miller with MSCs from human donors. Miller injected them into mice that had a version of MS.

“The mice got better, and quickly,” Miller said. And the animals didn’t reject the human cells or show negative effects.

The mice had fewer and smaller lesions on their myelin compared to control mice.

Miller and Caplan found evidence that the MSCs produced a barrier that blocked the autoimmune response and blocked formation of scar tissue, which would otherwise permanently halt signals. In addition, the cells produced molecules that enhanced regeneration of the damaged axon and rewrapping of the myelin around the axon.

Continued monitoring showed that one shot provided protection from the recurring disease for months.

Based on Caplan’s and Miller’s work, the university, Cleveland Clinic and University Hospitals Case Medical Center have begun a clinical trial. The first phase of the trial tests the safety of injecting MS patients with their own MSCs.